Nicotinic acid adenine dinucleotide phosphate (NAADP), a molecule derived f
rom beta -NADP, has been shown to trigger Ca2+ release from intracellular s
tores of invertebrate eggs and mammalian cell microsomes. NAADP-induced Ca2
+ release occurs through a mechanism distinct from that of inositol-1,4,5-t
risphosphate- or cyclic ADP-ribose-elicited Ca2+ release. This study invest
igated whether NAADP can be synthesized in rat kidney. Extracts from glomer
uli, mesangial cells, and papilla have high NAADP synthetic capacities. Con
versely, synthesis of NAADP in kidney cortex was almost undetectable. Furth
ermore, 9-cis-retinoic acid significantly upregulated NAADP synthesis in me
sangial cells. Authenticity of NAADP biosynthesis in glomeruli was affirmed
by HPLC analysis. NAADP stimulated Ca2+ release from mesangial cell micros
omes through a pathway distinct from that of inositol-1,4,5-trisphosphate o
r cyclic ADP-ribose. NAADP-triggered Ca2+ release may play an important rol
e in regulation of renal function.